Two autoimmune mouse strains, NZB and BXSB, have 40-48% incidence of cortical ectopias, and associated behavioral deficits. Research over the past five years has found that (1) left and right pawed ectopic mice differ on spatial and non-spatial associative learning tasks; (2) mice with autoimmunity have markedly depressed avoidance learning scores; (3) exposure to an enriched environment during early development facilitates learning in non-ectopic and ectopic mice, with some evidence that the non- ectopics profit more from the experience; and (4) the nature of the uterine environment (autoimmune or not) significantly influences the degree of autoimmunity of the offspring and subsequent avoidance learning. this proposal builds upon these findings and has the following purposes: (1) develop a set of higher-order learning tasks to more sharply distinguish those with biological anomalies (autoimmunity and ectopias); (2) investigate procedures for facilitating learning, including (i) extending early enrichment experiences, (ii) evaluating the effects of multiple learning experiences upon subsequent higher-order learning, and (iii) investigating whether administration of drugs will improve learning/memory; and (3) apply the techniques and procedures in (1) and (2) above to the experimental animals being investigated by the Anatomy and Immunology research components of this grant. The proposed research will produce an extensive behavioral characterization of animals prone to developing autoimmune disease with and without developmental brain anomalies; will do the same for subjects with induced autoimmunity or experimentally produced minor cortical malformations; and will determine the amount of learning improvement that can be expected in autoimmune and ectopic animals (both spontaneously occurring and experimentally produced) from environmental and pharmacological interventions, singly and jointly. These findings will add to our knowledge of the immune-defective mouse as a useful experimental model for specific developmental learning disabilities such as dyslexia.
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